Introduction
Cachexia is a word of Greek origin, derived from “kakos” (bad) and “hexis” (condition). Today, it is used in the literature to mean serious weight loss due to hunger or disease. It is expressed quantitatively when BMI is <18.5 kg/m2. In the course of recent life-threatening diseases (Cancer, AIDS, COPD, Multi-Organ Damage), >6% weight loss accompanied by a hypercatabolic state in the last 6 months is considered cachexia.
Cancer and Cachexia
The main problems expressed by cancer patients at the time of application are weakness-fatigue, pain, weight loss, loss of appetite, nausea-vomiting and shortness of breath. These depend on a number of factors produced by the tumor itself and the body, apart from the hypercatabolic process created by the tumor. Weight loss occurs in 30-80% of cancer cases during the course of the disease (Inui A., CA Cancer J Clin., 2002). The amount of weight loss and duration of development vary depending on the tissue affected, tumor type, size, and proliferation rate. Weight loss is very rapid in stomach and pancreatic tumors. The patient usually presents with extreme weight loss in the advanced stage. These are followed by lung, prostate and colon tumors. The disease stage parallels weight loss.
Proteolysis triggering factor and lipid mobilizing factor released by tumor cells cause excessive muscle destruction and lipolysis in the hypercatabolic process, which is oversynthesized by the body. Cytokines (TNF-alpha, IL-1, IL-6) contribute to this (Figure 1). A correlation has been detected between IL-6 level and disease stage, acute phase response and malnutrition status in lung cancer cases (Martín F. et.al., Cytokine. 1999). A relationship has been found between TNF-alpha, reduced oxygen products, reduced glutathione and vitamin E levels and the development of anorexia-cachexia syndrome (Fortunati N. et al., Oncol Rep. 2007). Circulating TNF levels were found to be higher and serum albumin and IGF-1 levels were found to be lower in those with >10% weight loss compared to others (Simons JP, et al., Clin Sci (Lond). 1999). A relationship between anorexia-cachexia syndrome and PTHrP levels has been determined, and it has been understood that when PTHrP is neutralized, weight loss stops and weight gain occurs. (Iguchi H, et al.,Int J Cancer. 2001). As in normal individuals, when the need for energy increases, glucose stores are initially used, and when the stores are emptied, the glucose cycle is initiated with proteolysis and lipolysis (gluconeogenesis) and muscle breakdown and weight loss occur. While serum CRP, fibrinogen, alpha-1 antitrypsin and ceruloplasmin levels increase, albumin, prealbumin and transferrin decrease. While leptin, synthesized from body fat tissues, causes a decrease in appetite and an increase in energy consumption at rest, ghrelin, synthesized in the gastrointestinal system, has the opposite effect. These two peptides act through their receptors on the hypothalamus. It is suggested that resistance develops at the hypothalamic receptor level in cancer patients, so that there is no increase in appetite in response to the increase in energy need.
Weight loss in cancer patients One of the most important reasons for weight loss is a decrease in food intake. Many factors cause this; loss of appetite (tumor burden, treatment, depression), early feeling of fullness (GIS), other GIS symptoms (nausea, vomiting), odynophagia (mocositis, fungal/viral esophagitis), dry mouth, dysphagia, difficulty in chewing, inability to access food as a result of decreased daily living activities, pain and deterioration in quality of life. Especially in tumors involving the gastrointestinal system, loss of appetite may occur as a result of poor oral hygiene, loss of teeth, space-occupying lesions, and side effects that occur during the course of the disease or due to the treatment used (radiotherapy acute/chronic effects, chemotherapy-mucositis). On the other hand, despite the initial articles about an increase in daily energy needs, subsequent studies did not confirm this information. There is no definitive evidence that resting energy needs are increased in cancer patients compared to healthy individuals. In a study, resting energy consumption was compared in cancer cases with and without weight loss, and no difference was found (Johnson G, et al., Nutrition, 2008). While resting energy consumption (RET) of cases with GI cancer and healthy individuals was found to be similar, these values were found to be similar in cases with pancreas and lung cancer. It has been found that it can increase. However, it was found that total energy consumption was lower than that of healthy individuals. is. It has been determined that there is a decrease in IET after chemotherapy and/or surgical resection in patients with small cell lung cancer. On the other hand, Heber and colleagues found the IET values of non-cachectic lung cancer cases to be at levels expected in healthy individuals, but they underlined in their comments that even normal values in these patients may indicate a hypermetabolic state (Heber D, et al., Cancer Res, 1996). p>
Cancer causes some changes in carbohydrate, lipid and protein metabolism. With the decrease in insulin sensitivity, impaired glucose tolerance develops, gluconeogenesis increases and serum lactate level increases. Lipolysis increases and serum triglyceride levels increase and lipoprotein lipase activity may decrease. Proteolysis-inducing factor, which is excessively secreted through the ubiquitin-proteasome pathway, causes excessive protein degradation, resulting in a negative nitrogen balance (Camps C, et al., Support Care Cancer, 2006).
Cancer treatment modalities can also cause cachexia. Malnutrition develops as a result of changes that occur in the acute or chronic period after radiotherapy, especially concerning the head and neck region. Diarrhea, malabsorption, stenosis and fistula may develop in abdominal radiotherapy applications. Surgical resection may cause secondary malabsorption. Pancreatic exocrine and endocrine insufficiency may occur as a result of pancreatic surgery. Malnutrition may develop due to side effects of chemotherapeutic drugs used in these patients. Vincristine, cisplatin and etoposide, which are drugs used in cases of small cell lung cancer, may cause malnutrition by causing electrolyte imbalance (cisplatin) secondary to nausea and vomiting, liver toxicity and renal tubulopathy. In non-small cell lung cancer, cisplatin and docetaxel may cause malnutrition for similar reasons.
Diagnosis
Anorexia-cachexia syndrome should be considered and treated quickly in the presence of clinical findings in cancer patients ( Figure 2). More importantly, malnutrition should be detected long before the patient reaches this state, and screening should even be performed to identify patients at nutritional risk. Today, nutritional screening NRS-2002 (Nutrition Risk Screening) can be done with a scoring system (Kondrup J, et al., Clin Nutr, 2003) (Figure 3). The patient's age, nutritional status and clinical disease diagnoses are scored. If the total score is ≥3, there is a nutritional risk. When the risk of malnutrition is detected, nutritional status can be evaluated with a more detailed test such as Subjective Global Assessment. There is data that plasma prealbumin level can be used in the evaluation of malnutrition. Since its plasma half-life is 2-3 days, it provides important information about the amount of food consumed recently. Prealbumin level above 0.17 g/dl is considered normal, between 0.17-0.10 g/dl is considered to be an increased risk, and <0.10 g/dl is considered to be a serious malnutrition risk. On the other hand, clinical conditions such as various chronic diseases, acute inflammatory events, infections and trauma that cause an acute phase reaction may reduce plasma levels (Myron JA, et al., Clin Chem Lab Med, 2007 & Shenkin A, Clin Chem, 2006). For this reason, it should be evaluated together with other acute phase reactants and used in the follow-up phase during the treatment of malnutrition rather than diagnosis.
Treatment
Nutritional support In patients to be treated, daily energy needs are first calculated. For this purpose, energy consumption at rest is calculated objectively (based on O2 consumption) using the calculation method (Harris Benedict Formula + Stress Factor + Activity Factor) (Figure 4) or indirect calorimetry. The appropriate supplement product and route of administration is selected according to caloric need and current clinical condition (Figure 5). In cases where it is not possible to feed orally or enterally or if the amount of enteral product is insufficient for more than 7 days, parenteral nutritional support treatment is applied. As a result, reaching the daily calorie target provides a significant increase in the survival time of patients (Bozzetti F, et al., Clin Nutr, 2009). Apart from this, the possibility of oral intake can be increased with treatments (oral care, anti-emetic, analgesic, antibiotic, anti-depressive) for the symptoms and mood disorders that are common in cancer cases (Figure 5). Supplement product; standard products, energy products, high protein, MCT (middle-chain triglycerides), glutamine-containing products and immunonutrition (ω-3 FA, RNA and arginine) products is selected from. Other supportive treatments include metoclopramide, 5-HT3 antagonists, cyproheptadine, corticosteroids, megestrol acetate (progestagen) and cannabinoid (dronabinol). As a result of research conducted in recent years, new treatment options are mentioned; Macrolide antibiotics, cytokine inhibitors, thalidomide and pentoxifylline. In a review of more than 50 studies on this subject in recent years, it was stated that steroids and progestins make a significant contribution to the treatment of anorexia (Yavuzsen T, et al., J Clin Oncol, 2005). In a study conducted with a lung cancer mouse model, melanocortin-4 receptor antagonists were found to stop tumor-induced cachexia (Chen C, et al., Bioorg Med Chem, 2008). In another study, weight gain and a decline in the acute phase response were detected in patients receiving ω-3 FA and ω-3 FA+celecoxib alone, and this response was more pronounced in the group receiving ω-3 FA+celecoxib (Cerchietti LC, et al., Nutr Cancer , 2007). Appetite increase was achieved in 95% of patients with oral megestrol acetate for two weeks (Tomiska M, et al., Neoplasma, 2003). Glutamine, one of the immunonutrition products, is known to be used in lymphocyte proliferation and cytokine synthesis in lymphocytes and macrophages, as well as being an energy substrate for immune system cells. Apart from these, it is used in DNA and RNA synthesis, suppresses the production of IL-8 and TNF, increases the phagocytosis ability of macrophages, increases the synthesis of anti-inflammatory factors (IL-10), plays a role in the organism's response to oxidative stress and contributes to the maintenance of intestinal mucosal integrity. In its deficiency, muscle breakdown accelerates, immune modulation is impaired, and widespread organ damage occurs in the presence of stress. Another immune nutrition product is arginine. There are still unclear data regarding its use in cancer cases.
Read: 0
